Hyaluronic acid (HA) is a glycosaminoglycan consisting of alternating D-glucuronic acid and N-acetyl-D-glucosamine units. The D-glucuronic acid and the N-acetyl-D-glucosamine are linked via a β (1→3) bond, while the N-acetyl-D-glucosamine and the D-glucuronic acid are linked via a β (1→4) bond. HA is abundant in the vitreous humor of the eye, the synovial fluid of articular joints, and the extracellular matrix. Due to its innate biocompatibility and unique physical properties, HA has been used for delivery of drugs, preparation of a biocompatible material, artificial tears for xerophthalmic patients, and a substances for relieving symptoms of osteoarthritis.
The presence of HA in human saliva has been reported and HA in saliva may contribute to the lubricating and healing properties of saliva, and assisting in protecting the oral mucosa. HA has also been reported to display anti-Candida activity. Due to its viscoelastic properties and non-immunogenicity, it is known that HA may be considered as a candidate for substitution of xerostomic patients saliva, and shows similar physical properties to human saliva at a certain concentration.
The relation between the reduction of HA in the saliva and the occurrence of xerostomia is known, which proves that HA serves to protect and lubricate the oral mucosa. In addition, the wound healing activity and the potential anti-Candida activity of HA may provide an additional advantage to patients suffering from dry mouth who are vulnerable to oral mucosal injuries and candidiasis.
There have been attempts to strengthen and recover an antimicrobial ability of saliva using commercially available oral hygiene products. Antimicrobial proteins most widely used in the oral hygiene products include lysozyme and lactoperoxidase. The antimicrobial proteins were introduced into a saliva substitute to recover the antimicrobial ability of the saliva of a patient suffering from dry mouth, who was vulnerable to candidiasis. The antifungal activities of the lysozyme and the antifungal activities of the peroxidase system are known. It is known that lysozyme and peroxidase were used together to increase the Candida-killing activity. It has not been confirmed that the in vitro experimental results were applied to an in vivo environment in the same manner, but the antimicrobial supplements may reduce development of candidiasis in xerostomic patients.
The oral cavity provides an environment where saliva substitutes and saliva molecules can be present at the same time. Therefore, the HA molecules of the saliva substitutes will also interact with the antimicrobial molecules of human saliva. The presence of an HA-lysozyme complex (Van Damme et al. Binding of Hyaluronan to Lysozyme at Various PHSA, Biochemistry International, 1991 July 24(4), 605-13; Van Damme et al. Binding Properties of Glycosaminoglycans to Lysozyme-Effect of Salt and Molecular Weight, Archives of Biochemistry and Biopbysics, 1994 April, 310(1), 16-24; Moss et al. Dependence of Salt Concentration on Glycosaminoglycan-Lysozyme Interactions in Cartilage, Archives of Biochemistry and Biophysics, 1997 Dec. 1, 348(1), 49-55) and the HA-peroxidase complex (Green et al. Depolymerization of Synovial Fluid Hyaluronic Acid (HA) by the Complete Myeloperoxidase (MPO) System May Involve the Formation of a HA-MPO Ionic Complex, The Journal of Rheumatology, 1990, 17:12, 1670-5) was proposed in the prior-art literatures.
However, it is not known how and what HA affects the anti-Candida activities of lysozyme and peroxidase.